Opioid agonists relieve pain by acting on receptors in the central nervous system. However, systemically acting opioids have a number of side effects such as sedation, respiratory depression, nausea, and constipation. An alternative approach to pain control is to apply topically acting drugs to the peripheral site of origin of the pain. Topical drugs used to control pain will act locally on damaged or dysfunctional soft tissues or peripheral nerves. Topical delivery systems differ from transdermal delivery systems in that they target a site immediately adjacent to the site of delivery rather than using the skin as an alternate systemic delivery system. Their actions may be on the inflammatory response itself or on sensory neurons.
Opioids bind to specific opioid receptors in the central nervous system. There are three principal classes of opioid receptors, i.e. μ, κ and δ opioid receptors. These opioid receptors are usually not found in normal tissue and hence topical administration of opioids has not been discussed intensively.
U.S. Pat. No. 6,787,149, which is one of the few reports on topical opioid application, discloses a pharmaceutical composition which comprises an admixture of an opioid agonist agent and a pharmaceutically acceptable excipient for topical administration to inflamed skin or mucosal tissue. Topical excipients listed in U.S. Pat. No. 6,787,149 comprise creams, ointments, gels or petrolatum.
G. Watterson et al., Arch. Dis. Child., 2004, 679-681, disclose the use of topical morphine gel in the treatment of children with epidermolysis bullosa, where acute inflammatory pain is a major symptom.
A. Welling, Emerg. Med. J., 2007, 408-412, discusses the agonist efficacy of topical morphine on superficial burns. A gel comprising morphine sulfate was administered.
Skin lesions, e.g. resulting from burns or ulcers, may cover larger skin areas. However, the larger the wound area that needs topical treatment, the higher is the risk of systemic absorption. Thus, for the treatment of skin lesions, in particular those covering a larger skin area, there is a continuing need for pharmaceutical compositions that allow topical treatment and at the same time prevent systemic absorption as much as possible.